AbstractBackgroundUS guidelines recommend genotype testing at human immunodeficiency virus (HIV) diagnosis (“baseline genotype”) to detect transmitted drug resistance (TDR) to nonnucleoside reverse transcriptase inhibitors (NNRTIs), nucleoside reverse transcriptase inhibitors (NRTIs), and protease inhibitors. With integrase strand inhibitor (INSTI)-based regimens now recommended as first-line antiretroviral therapy (ART), the of baseline genotypes is uncertain.MethodsWe used the Cost-effectiveness of Preventing AIDS Complications model to examine the clinical impact and cost-effectiveness of baseline genotype compared to no baseline genotype for people starting ART with dolutegravir (DTG) and an NRTI pair. For people with no TDR (83.8%), baseline genotype does not alter regimen selection. Among people with transmitted NRTI resistance (5.8%), baseline genotype guides NRTI selection and informs subsequent ART after adverse events (DTG AEs, 14%). Among people with transmitted NNRTI resistance (7.2%), baseline genotype influences care only for people with DTG AEs switching to NNRTI-based regimens. The 48-week virologic suppression varied (40%–92%) depending on TDR. Costs included $320/genotype and $2500–$3000/month for ART.ResultsCompared to no baseline genotype, baseline genotype resulted in <1 additional undiscounted quality-adjusted life-day (QALD), cost an additional $500/person, and was not cost-effective (incremental cost-effectiveness ratio: $420 000/quality-adjusted life-year). In univariate sensitivity analysis, clinical benefits of baseline genotype never exceeded 5 QALDs for all newly diagnosed people with HIV. Baseline genotype was cost-effective at current TDR prevalence only under unlikely conditions, eg, DTG-based regimens achieving ≤50% suppression of transmitted NRTI resistance.ConclusionsWith INSTI-based first-line regimens in the United States, baseline genotype offers minimal clinical benefit and is not cost-effective.